TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20574	61945;61946;61947	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
N2AB	18933	57022;57023;57024	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
N2A	18006	54241;54242;54243	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
N2B	11509	34750;34751;34752	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
Novex-1	11634	35125;35126;35127	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
Novex-2	11701	35326;35327;35328	chr2:178590005;178590004;178590003	chr2:179454732;179454731;179454730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-37
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3099
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Q/R	rs1176666570	-0.435	0.99	N	0.589	0.327	0.227934060464	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Q/A	0.3558	ambiguous	0.3825	ambiguous	-0.623	Destabilizing	0.993	D	0.625	neutral	None	None	None	None	N
Q/C	0.6658	likely_pathogenic	0.6869	pathogenic	0.068	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Q/D	0.7534	likely_pathogenic	0.7611	pathogenic	-0.692	Destabilizing	0.971	D	0.573	neutral	None	None	None	None	N
Q/E	0.1333	likely_benign	0.1342	benign	-0.585	Destabilizing	0.953	D	0.468	neutral	N	0.451043088	None	None	N
Q/F	0.8226	likely_pathogenic	0.8284	pathogenic	-0.183	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
Q/G	0.413	ambiguous	0.4263	ambiguous	-1.002	Destabilizing	0.985	D	0.691	prob.neutral	None	None	None	None	N
Q/H	0.4035	ambiguous	0.4146	ambiguous	-0.899	Destabilizing	0.997	D	0.579	neutral	N	0.518750948	None	None	N
Q/I	0.4519	ambiguous	0.4452	ambiguous	0.355	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Q/K	0.1242	likely_benign	0.1239	benign	-0.603	Destabilizing	0.98	D	0.557	neutral	N	0.494276578	None	None	N
Q/L	0.186	likely_benign	0.1912	benign	0.355	Stabilizing	0.99	D	0.665	neutral	D	0.524599484	None	None	N
Q/M	0.4394	ambiguous	0.4437	ambiguous	0.785	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	N
Q/N	0.4934	ambiguous	0.4905	ambiguous	-1.036	Destabilizing	0.469	N	0.326	neutral	None	None	None	None	N
Q/P	0.65	likely_pathogenic	0.73	pathogenic	0.06	Stabilizing	0.999	D	0.681	prob.neutral	D	0.524946201	None	None	N
Q/R	0.1239	likely_benign	0.1272	benign	-0.584	Destabilizing	0.99	D	0.589	neutral	N	0.446367987	None	None	N
Q/S	0.4268	ambiguous	0.4279	ambiguous	-1.107	Destabilizing	0.985	D	0.555	neutral	None	None	None	None	N
Q/T	0.2966	likely_benign	0.3122	benign	-0.815	Destabilizing	0.985	D	0.643	neutral	None	None	None	None	N
Q/V	0.29	likely_benign	0.3001	benign	0.06	Stabilizing	0.999	D	0.653	neutral	None	None	None	None	N
Q/W	0.7914	likely_pathogenic	0.8011	pathogenic	-0.128	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Q/Y	0.6625	likely_pathogenic	0.6718	pathogenic	0.07	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.